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Biomedical subjects

X Guo

Publications and source records attributed to X Guo.

At least 307 records · Page 17Linked to original sources
PubMed1997

Osteopenia in adolescent idiopathic scoliosis. A primary problem or secondary to the spinal deformity?

STUDY DESIGN: A cross-sectional study to assess the lumbar spinal and proximal femoral bone mineral density in girls aged 12, 13, or 14 years with adolescent idiopathic scoliosis and to compare them with bone mineral densities of an age-matched control group. OBJECTIVES: To determine whether there is an association of osteopenia with idiopathic scoliosis, to compare bone mineral density in patients with scoliosis in different age groups with healthy controls, and to correlate bone mineral density with scoliotic parameters, including the pattern and magnitude of the curve. SUMMARY OF BACKGROUND DATA: Routine radiographs allow very limited assessment of osteopenia. Therefore, only a few studies have compared osteopenia in patients with scoliosis with that in healthy individuals. New techniques allow a more reliable quantification of the bone mineral state in adolescent idiopathic scoliosis. Available series in the literature either had a small sample population with inadequate controls or examined a large age range. METHODS: Using a dual energy x-ray absorptiometer, bone mineral density was measured in the predominant trabecular bone area, i.e., the lumbar spine (L2-L4) and bilateral proximal femur, in 81 girls aged 12, 13, or 14 years old with idiopathic scoliosis of various degrees of severity. Results were compared with those of 220 age-matched healthy control girls. RESULTS: In all three age groups, scoliotic patients had significantly lower bone mineral density in all measured regions than that in the control individuals (student's t test). Sixty-eight percent of the scoliotic individuals had a significantly reduced bone mineral density. Differences in bone mineral density between bilateral hips (paired t test) were not statistically significant either in scoliotic patients or in healthy control individuals. No differences in body weight, body height, or menarche status were found between the scoliotic and control individuals. Correlation studies showed that, in scoliotic patients, the values of bone mineral density did not correlate with the curve degree or curve pattern. CONCLUSIONS: There is a persistently lower bone mineral density in patients between 12 years and 14 years of age with idiopathic scoliosis. The decreased bone mineral density occurred in patients with idiopathic scoliosis before the age of 12 years, with no further progression from the age 12 to age 14, and did not correlate with the scoliosis degree or pattern. These findings suggest that the osteopenia in idiopathic scoliosis may be related to the primary etiology of the disease rather than secondary to the asymmetrical mechanical forces associated with the back deformities.

Absorptiometry, Photon↗
PubMed1997

Cyclic ADP-ribose-gated Ca2+ release in sea urchin eggs requires an elevated.

Cyclic ADP-ribose (cADPr) has been shown to release intracellular Ca2+ from sea urchin eggs and a variety of vertebrate cell types, although its mechanism of action remains elusive. We employed the caged version of cADPr to study the [Ca2+] transient kinetics in intact sea urchin eggs for insights into how cADPr gates Ca2+ release. Ca2+ release triggered by photolytic production of cADPr was initially slow, with an effective delay of several hundred milliseconds before the onset of a rapid Ca2+ release phase. In contrast, Ca2+ release induced by photolysis of caged inositol 1,4,5-trisphosphate was immediate in onset and roughly an order of magnitude faster. The delay before cADPr-induced Ca2+ release was eliminated when the [Ca2+] was step-elevated coincident with the photoliberation of cADPr and greatly prolonged in the presence of exogenous Ca2+ buffers. Thus, the slow onset of Ca2+ release does not reflect an intrinsically slow rate by which cADPr gates release channels. Rather, a [Ca2+] rise from resting levels is needed to achieve more than minimal cADPr activity. Full release of Ca2+ by cADPr in intact sea urchin eggs requires a positive Ca2+ feedback.

Adenosine Diphosphate Ribose↗
PubMed1997

Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts.

BACKGROUND: Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. METHODS AND RESULTS: The hearts of young adult rats (12 weeks old: group Y, n = 44) and middle-aged rats (50 weeks old: group M, n = 44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 20 (group Y, n = 22) or 15 (group M, n = 22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1; creatine phosphate, 17.0 to 23.1 mumol/g dry wt) and reduced left ventricular end-diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 mumol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion-induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M. CONCLUSIONS: These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.

Adenosine Triphosphate↗
PubMed1997

Neurophysiological signs of cocaine dependence: increased electroencephalogram beta during withdrawal.

To determine whether a central nervous system marker of cocaine dependence might exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent men (DSM-III-R criteria) was compared with two control groups [nondrug group (n = 10) and drug group who abused drugs, but were not cocaine dependent (n = 20)]. The EEG was recorded from eight sites after about 10 days of monitored abstinence (range 4-15 days) on a closed research ward for the drug-using individuals. The EEG was recorded for the nondrug control group as outpatients. The drug history was determined by the drug history questionnaire and a medical screening interview. The percent of EEG beta activity for the cocaine-dependent subjects was greater than that of both control groups (p < .05) as well as a normative database (HZI: Tarrytown, NY). The percent of EEG beta in frontal and central areas of the cocaine-dependent individuals was correlated with the frequency of cocaine use during the last 30 days. High levels of EEG beta may be a neurophysiological withdrawal sign in cocaine-dependent men.

Adult↗
PubMed1997

Immunomodulation and enhancement of antitumor activity by co-administration of 1,3-bis(2-chloroethyl)-1-nitrosourea and thymidine.

The antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been shown previously to be enhanced markedly by the co-administration of pyrimidine deoxyribonucleosides (Lin and Prusoff, Cancer Res 47: 394-397, 1987). In the present study, we examined the cellular mechanisms underlying the augmentation effect of thymidine, one of the pyrimidine deoxyribonucleosides. It was found that thymidine did not increase the cytotoxicity of BCNU for B16/F10 melanoma cells in vitro. Instead, thymidine appeared to produce modulatory actions on the immune system of the tumor-bearing mice. More than 40% of the BCNU/ thymidine-cured mice specifically rejected secondary rechallenge with the B16/F10 tumor. Furthermore, these cured mice developed extensive depigmentation of their natural black hair, suggesting immune reactions to normal melanocytes. When spleen cells from normal mice were treated with BCNU alone, their response to T-cell mitogen phytohemagglutinin was suppressed markedly. This suppression was ablated by co-administration of BCNU with thymidine. Such BCNU/thymidine treatment also augmented the activity of tumor-specific cytotoxic T-cells in tumor-bearing mice. Taken together, these results suggest that the enhanced antitumor activity of combined BCNU and thymidine may result from the action of thymidine on the immune effector mechanisms, which facilitate the development of antitumor immune responses in the presence of immunosuppression induced by BCNU.

Adjuvants, Immunologic↗
PubMed1997

Pharmacological evidence that calcium is not required for P2-receptor-stimulated Cl- secretion in HT29-Cl.16E.

Extracellular ATP at micro- to millimolar concentrations activates Cl- conductance and increases cytosolic calcium ([Ca]i) in many epithelial cells, including the colonic epithelial cell line HT29-Cl. 16E. Therefore, [Ca]i has been postulated to be the intracellular messenger for Cl- channel activation. HT29-Cl.16E is a highly differentiated cell line that forms confluent monolayers and secretes mucins and Cl-. The involvement of [Ca]i in the purinergically-stimulated Cl- secretion was investigated pharmacologically in this cell line by whole-cell patch-clamp and Ussing chamber techniques, as well as [Ca]i measurements in fura-2 loaded cells. The calmodulin inhibitors W13 (5 microm) and chlorpromazine (50 microm) abolished increases in ATP-stimulated [Ca]i-increases by 90% and 80%, respectively. However, these inhibitors had no effect on the ATP-stimulated Cl- conductance measured in either individual cells or confluent monolayers. As controls, the effects of W13 and chlorpromazine on Ca2+-ionophore stimulated Cl- conductance was measured. In this case, the two compounds inhibited whole cell Cl- conductance and monolayer Isc by 90% and 100%, respectively. These data demonstrate: (1) The purinergically-stimulated increase in Cl- current does not require an increase in [Ca]i, suggesting the involvement of either another signaling pathway or direct activation of Cl- channels by purinergic receptors. (2) A calmodulin or a calmodulinlike binding site that is sensitive to W13 and chlorpromazine participates in the regulation of the [Ca]i increase by purinergic receptors in HT29-Cl.16E.

Calcium↗
PubMed1997

Amino-terminal epitopes are exposed when full-length open reading frame 2 of hepatitis E virus is expressed in Escherichia coli, but carboxy-terminal epitopes are masked.

We constructed a panel of overlapping and non-overlapping fragments of cDNA derived from open reading frame 2 (ORF2) of hepatitis E virus (HEV) and fused to the gene encoding glutathione S-transferase (GST), from which proteins were expressed in Escherichia coli. IgG-specific immunoreactivity against each protein was measured by Western immunoblotting using sera from experimentally infected Rhesus macaques (Macaca mulatta) or from HEV-infected patients. Under these conditions, full-length ORF2 protein (GST-ORF2) was strongly reactive with acute-phase sera from either macaques or patients, but was poorly reactive with convalescent sera. Recombinant protein GST-ORF2.3, representing amino acids 1-110 of the 660 encoded by ORF2, demonstrated a pattern of reactivity largely indistinguishable from the full-length protein. Conversely, GST-ORF2.1, representing amino acids 394-660 of the ORF2 protein was strongly reactive with both acute- and convalescent-phase sera. Extension of GST-ORF2.1 towards the N-terminus led to a progressive loss of convalescent-phase reactivity, apparent with as few as 20 additional HEV-specific amino acids. Deletion of 40 or more amino acids from the N-terminus of ORF2.1 also led to reduced convalescent-phase reactivity, however a protein representing this "reactive" region, containing amino acids 394-473, was poorly reactive, suggesting that the convalescent-reactive epitopes are conformational. Expression of full-length ORF2 protein in E. coli therefore masks the convalescent-reactive epitopes within the C-terminal part of the protein, without affecting N-terminal, acute-reactive epitopes.

Animals↗
PubMed1997

Molecular cloning of a novel 97-kd Golgi complex autoantigen associated with Sjögren's syndrome.

OBJECTIVE: To identify a Golgi complex autoantigen bound by Sjögren's syndrome (SS) autoantibodies. METHODS: Serum from a patient with secondary SS and anti-Golgi antibodies was used as a probe to isolate a complementary DNA (cDNA) insert from a HeLa cDNA library. RESULTS: A 3.7-kb cDNA encoding a 56-kd recombinant protein was immunoprecipitated by the human anti-Golgi serum and immune rabbit serum. Western blot analysis showed that the immune rabbit sera recognized a protein of 97 kd (golgin-97), suggesting that the isolated clone contained a partial cDNA. The 5' upstream sequence was obtained by rapid amplification of the cDNA ends. The complete cDNA contained 4,860 basepairs, encoding a protein with a calculated Mr of 88 kd. Antibodies to golgin-97 were found in 12 (20%) of 60 sera known to have anti-Golgi autoantibodies, and the majority of these sera (8 of 12, or 75%) were from patients who had secondary SS. CONCLUSION: Golgin-97 is a unique Golgi complex antigen that appears to be a target of SS autoantibodies.

Adult↗
PubMed1997

Selenium-induced growth reduction in Brassica land races considered for phytoremediation.

Brassica species considered for use in selenium (Se) phytoremediation need to accumulate large amounts of Se to be successful. Retarded plant growth and impaired protein synthesis are common symptoms for plants grown under seleniferous soils. Selenium accumulation by different land races of Brassica juncea (L.) Czern and Coss and one land race of Brassica carinata was investigated in Se-enriched water and soil cultures containing 2 mg Se kg-1. Effects of Se concentration in the root environment on the assimilation of Se, leaf surface area, dry matter yield, total leaf protein concentration, and free seleno-amino acid concentrations were analyzed for plants grown in Se-laden media. In water culture, shoot Se concentrations among the land races ranged from 501 to 1017 mg Se kg-1 dry matter (DM), and in plants grown in Se-laden soil, concentrations ranged from 407 to 769 mg Se kg-1 DM. Land races grown with Se exhibited decreases in dry matter yields from 12 to 23% and in leaf surface area from 5 to 26% compared to the same land races grown without Se. Protein content was significantly correlated both with shoot Se concentrations (r = 0.746, P < 0.001) and with leaf surface area (r = 0.446, P < 0.01) for all land races grown in Se-enriched water culture. There was also a significant correlation (r = 0.767, P < 0.001) between total Se assimilation and shoot protein for all land races. Free selenomethionine was detected for plants grown with Se and ranged from 92 to 958 ng g-1 DM. Other seleno-amino acids, Se-methyl-selenocysteine and selenocysteine, were not consistently detected as free amino acids in the different land races. Although visual symptoms of Se toxicity were not observed in the Brassica species, dry matter yield, leaf surface, and total shoot protein decreased, depending on the land races tested.

Amino Acids↗
PubMed1997

Effects of elevated selenium and salinity concentrations in root zone on selenium and salt secretion in saltgrass (Distichlis spicata L.).

The effects of elevated selenium (Se) and salinity concentrations in the root zone on Se and salt secretion and accumulation were studied for an inland (Kesterson) and a coastal (Bodega Bay) saltgrass in sand culture and under greenhouse conditions. The results of this study indicate that the secretory mechanism of the saltgrass exhibits high ion specificity. Plants of both ecotypes were more efficient at Cl- and Na+ secretion than at SO4(2-) and Se secretion, suggesting that the saltgrass secretion mechanism is adapted primarily to saline environments high in NaCl. The saltgrass plants of the Kesterson ecotype secreted more Se than the Bodega Bay plants when treated with Se alone. However, the Bodega Bay plants secreted more Se than the Kesterson plants when the plants were treated with Se+NaCl. These differences reflect a ecotypical difference in which the Kesterson plants are more adaptive to the seleniferous soil, and the Bodega Bay plants are more adaptive to a coastal saline soil high in NaCl. Sulfate availability inhibited both Se accumulation and Se secretion in the plants of both ecotypes by approximately 98%. Ion secretion molar ratios of Na:Cl were calculated and the results suggest that Na+ secretion is dependent on the availability of Cl-. Selenium was taken up by plants with little discrimination, and thus it may be regarded as a master of chemical mimicry sharing similar physical and chemical properties with sulfur (S). Selenium and salt accumulation indices and secretion efficiency indices were calculated and found that the accumulation indices were higher for Se than for S, suggesting that Se uptake may be more passive and less regulated by active transport than S. Secretion efficiency was much higher for Na+ and Cl- than for Se and SO4(2-), but the efficiency indices between ecotypes were comparable, suggesting that the secretion mechanism in this species is designed mainly for adaptation of high NaCl concentrations. About 85% of the secreted Se was found in selenate form. This finding suggests that the mechanism of Se translocation and Se secretion in the saltgrass resembles the movement of selenate in xylem found in nonhalophytic plants. Less than 15% of organic Se was detected in the secretions and only trace amount of selenite was detected. Overall, the Se secretion mechanism in saltgrass does not seem to contribute substantial Se speciation in the plant soil system.

Poaceae↗
PubMed1997

Decrease in ischemic tolerance with aging in isolated perfused Fischer 344 rat hearts: relation to increases in intracellular Na+ after ischemia.

While the ischemic tolerance of the myocardium has been reported to decrease with senescence, it is not known when and how this occurs. Our objectives were to determine whether the tolerance to myocardial ischemia in rats decreased before the onset of senescence and whether an increase in myocardial ionic imbalance was associated with an enhanced myocardial injury with aging. Hearts were isolated from Fischer 344 rats categorized as young (12 weeks old), mature adult (24 weeks), middle-aged (50 weeks) or senescent (100 weeks). Hearts were perfused isovolumically by the Langendorff procedure and subjected to 25 min of global ischemia followed by 30 min of reperfusion. In the 50- and 100-week-old rats, the recovery of ventricular function and high-energy phosphate levels was lower and there was increased incidence of ventricular fibrillation after 25 min of global ischemia followed by reperfusion. The release of creatine kinase and lactate dehydrogenase during reperfusion was greater in the 50-and 100-week-old rats than in the 12- and 24-week-old rats, indicating the irreversible myocardial damage due to ischemia-reperfusion increased by middle-age. Intracellular levels of Na+ and K+ before ischemia were higher in the 50- or 100-week-old rats than in the 12-week-old rats. The increase in intracellular Na+ at end of ischemia was greater in the older (50-week-old, 215% of the pre-ischemic value; 100-week-old, 232% of the pre-ischemic value) than in the younger rats (12-week-old, 158% of the pre-ischemic value). Results indicated that the rat heart becomes more vulnerable to ischemia in middle-age. This decrease in ischemic tolerance may be caused by an acceleration of myocardial ionic imbalance with aging.

Aging↗
PubMed1997

Local inotropic stimulation by methylene blue does not improve mechanical dysfunction due to myocardial stunning.

We tested the hypothesis that reduction of intramyocardial cyclic guanosine monophosphate (GMP) by methylene blue (MB) would improve mechanical dysfunction in stunned myocardium. Regional stunning was produced in nine open-chest anesthetized dogs by a 12-min left anterior descending coronary artery (LAD) occlusion. MB was infused into the LAD during reperfusion (1 mg/kg per min). Stunning reduced LAD force development, introduced a significant time delay between the onset of force and shortening (delay) and caused significant systolic bulging to occur. Stunning reduced systolic regional work (the integrated product of force and segment shortening during systole), but did not significantly alter regional oxygen consumption or cyclic GMP levels. MB decreased cyclic GMP (1.8 +/- 0.2 to 0.9 +/- 0.1 pmol/g) and increased peak force (36 +/- 5 to 55 +/- 10 g). However, MB increased delay (93.9 +/- 18.4 to 233 +/- 19 ms) and systolic bulging (5.9 +/- 2.1% to 9.3 +/- 2.8%) and further reduced systolic regional work (control; 4204 +/- 933 g x mm/min; stunned: 2191 +/- 542 g x mm/min; MB: 1153 +/- 516 g x mm/min). MB increased regional myocardial oxygen consumption (7.4 +/- 1.0 to 15.6 +/- 2.7 ml O2/min per 100 g). These results suggest that depressed contractility, while present in myocardial stunning, is not the primary cause of mechanical dysfunction.

Animals↗
PubMed1997

Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis.

BACKGROUND & AIMS: Urokinase plasminogen activator (uPA) regulates plasmin generation from plasminogen. The aim of this study was to analyze the role of the plasminogen activator/plasmin system in chronic pancreatitis (CP). METHODS: Using Northern blot analysis, in situ hybridization, and immunohistochemistry, the expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) was studied in 14 patients undergoing pancreatic resection for CP. Normal control pancreatic tissue was obtained through an organ donor program. RESULTS: Eight of 14 CP samples showed concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold), and TGF-beta 1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI-1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in situ hybridization, moderate to strong mRNA staining of all four factors was present in acinar cells, some ductal cells, and areas with ductal metaplasia in CP samples. A similar staining pattern was found by immunohistochemistry. Intense mRNA and immunostaining for all of these factors in CP samples was associated with a higher degree of pancreatic damage. CONCLUSIONS: uPA and its receptor may contribute to the lytic damage observed in CP by plasmin generation. Similarly, increased amounts of plasmin may activate latent TGF-beta, thereby leading to the accumulation of fibrotic tissue.

Adolescent↗
PubMed1997

Dual actions of (-)-stepholidine on the dopamine receptor-mediated adenylate cyclase activity in rat corpus striatum.

(-)-Stepholidine (SPD) is an antagonist of normosensitive dopamine (DA) receptors, but it exhibits D1 agonistic action on rotational behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNC). In the present study, agonistic and antagonistic effects of SPD on the DA receptor-mediated synaptosomal adenylate cyclase (AC) activity in rat striatum were investigated. After blockade of D2 receptors, SPD augmented AC activity dose-dependently. The EC50 value was 41.1 +/- 8.6 micromol/L. At the concentration of 10 micromol/L, SPD increased cAMP formation from a basal level (50.8 +/- 10.3 pmol/mg protein/min) to 133.7 +/- 31.8 pmol/mg protein/min. The SPD-induced stimulation of AC activity was almost completely reversed by 10 micromol/L Sch23390. These results indicate that SPD possesses an agonistic action on the D1 receptor. Forskolin-stimulated adenylate cyclase (FSAC) activity was used as a model to elucidate the effect of SPD on D2 receptors. The results indicate that DA inhibited FSAC activity dose-dependently, while SPD partially restored FSAC activity. Taken together, these results support the conclusion that SPD has dual actions on DA receptors that mediate AC activity, i.e., an agonistic action on D1 receptors and an antagonistic action on D2 receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1997

Isolation of a functional ecdysteroid receptor homologue from the ixodid tick Amblyomma americanum (L.).

Ecdysteroids are assumed to be the major steroid hormones in arthropods. However, with the exception of insects and crustaceans, very little is known about ecdysteroid action in other arthropods. To determine if ecdysteriods play a functional role in the ixodid tick, Amblyomma americanum (L.), we isolated cDNAs encoding three presumed ecdysteroid receptor isoforms (AamEcRA1, AamEcRA2, and AamEcRA3) that have common DNA and ligand binding domains linked to distinct amino termini. The DNA and ligand binding domains share an average of 86 and 64% identity, respectively with DNA and ligand binding domains from insect EcR proteins. The amino termini are highly divergent and the AamEcRs lack the 'F' domain found in the insect EcRs. Analysis of AamEcR cDNAs show that processing of the AamEcR gene is complex, producing multiple transcripts with unique 5' and 3' termini as well as splicing variants with incomplete open reading frames. AamEcR mRNA profiles in whole animals and isolated tissues are consistent with complex regulation of AamEcR expression. We also examined the ability of AamEcRA1, when paired with an AamRXR, to activate transcription of an ecdysone response element containing reporter, and demonstrate that the AamEcR gene encodes a functional ecdysteroid receptor.

Amino Acid Sequence↗
PubMed1997

Presence of two signaling TGF-beta receptors in human pancreatic cancer correlates with advanced tumor stage.

Transforming growth factor-beta (TGF-beta) signal transduction is mediated via specific cell surface signaling TGF-beta receptors, most notably the type I ALK5 (TbetaR-I[ALK5]) and the type II (TbetaR-II). We evaluated TbetaR-I(ALK5) and TbetaR-II expression in 41 human pancreatic cancer tissue samples and correlated these findings with clinical data of the patients. Northern blot analysis indicated that, in comparison with the normal pancreas, pancreatic adenocarcinomas exhibited 8.0-fold and 4.5-fold increases (P < 0.01), respectively, in mRNA levels encoding TbetaR-I(ALK5) and TbetaR-II. In situ hybridization showed that both TbetaR-I(ALK5) and TbetaR-II mRNA were highly expressed in the majority of pancreatic cancer cells. Immunohistochemical analysis of TbetaR-I(ALK5) and TbetaR-II revealed positive immunostaining in 73% and 56% of the tumors, respectively. Both receptors were concomitantly present in 54% of the pancreatic cancer samples. The presence of TbetaR-I(ALK5) or TbetaR-II and the concomitant presence of TbetaR-I(ALK5) and TbetaR-II in the cancer cells was associated with advanced tumor stage (P < 0.01). These findings show that in many human pancreatic cancers, increased levels of the two signaling TbetaRs are present. The presence of the signaling TbetaRs in advanced tumor stages indicates a role in disease progression.

Adenocarcinoma↗
PubMed1997

Thermal injury induces the development of inflammatory macrophages from nonadherent bone marrow cells.

The normal course of hematopoiesis is controlled by growth factors and cytokines and, therefore, should be susceptible to alterations induced by systemic mediator release such as that seen following thermal injury. We hypothesized that a brief exposure of developing macrophages to the postthermal injury state would result in functionally altered progeny. We measured the production of inflammatory mediators by rat, bone-marrow macrophage precursors harvested 24 h following a 30% TBSA burn after subsequent maturation in a controlled, in vitro environment. Interleukin (IL)-6, tumor necrosis factor (TNF), and prostaglandin (PG) E2 levels in response to 24 h stimulation with lipopolysaccharide (LPS) were measured following 4 or 8 days of incubation with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or both. Flow cytometric analysis showed that bone marrow cells harvested from burn and sham animals cultured in GM-CSF developed principally into macrophages (His48+, R21A6A+, CD11b+. Unstimulated cells produced negligent levels of cytokines and PGE2. Stimulated burn-derived cells released greater amounts of IL-6 and TNF at 4 or 8 days of culture depending on the conditions. Elevated PGE2 release was noted in all GM-CSF containing cultures, with burn-derived cells showing a trend towards reduced prostaglandin release. Detection of mRNA for cytokines after LPS stimulation showed no change in IL-6 or TNF transcripts. A short exposure to the systemic effects of thermal injury preprogramed macrophage progenitor cells with the propensity to develop into inflammatory macrophages, secreting higher levels of TNF and IL-6. This shift towards proinflammatory functions in these cells suggests they could be a source of enhanced inflammatory mediator release at 4 or more days post thermal injury.

Animals↗